Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways.
G(12/13) or G(q) signaling pathways activate platelet GPIIb/IIIa when combined with G(i) signaling. We tested whether combined G(i) and G(z) pathways also cause GPIIb/IIIa activation and compared the signaling requirements of these events. Platelet aggregation occurred by combined stimulation of G(i) and G(z) pathways in human platelets and in P2Y1-deficient and G alpha(q)-deficient mouse platelets, confirming that the combination of G(i) and G(z) signaling causes platelet aggregation. When G(i) stimulation was combined with G(z) stimulation, there was a small mobilization of intracellular calcium. Chelation of intracellular calcium decreased the extent of this platelet aggregation, whereas it abolished the G(q) plus G(i)-mediated platelet aggregation. Costimulation of G(i) plus G(z) pathways also caused thromboxane generation that was dependent on outside-in signaling and was inhibited by PP2, a Src family tyrosine kinase inhibitor. Src family tyrosine kinase inhibitors also inhibited platelet aggregation and decreased the PAC-1 binding caused by costimulation of G(i) and G(z) signaling pathways in aspirin-treated platelets. However, Src family kinase inhibitors did not affect G(q) plus G(i)-mediated platelet aggregation. We conclude that the combination of G(i) plus G(z) pathways have different requirements than G(q) plus G(i) pathways for calcium and Src family kinases in GPIIb/IIIa activation and thromboxane production.[1]References
- Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways. Dorsam, R.T., Kim, S., Murugappan, S., Rachoor, S., Shankar, H., Jin, J., Kunapuli, S.P. Blood (2005) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
